A Genetic Susceptibility Study of Lung Cancer Risk Potentially Associated with Polycyclic Aromatic Hydrocarbon Inhalation Exposure.

To establish a genetic susceptibility assessment model of lung cancer risk potentially associated with polycyclic aromatic hydrocarbon (PAH) inhalation exposure among non-smokers in China, a total of 143 patients with lung adenocarcinoma and 143 cancer-free individuals were recruited. Sixty-eight genetic polymorphisms in 10 pathways related to PAH metabolism and tumorigenesis were selected and examined. It was observed that 3 genetic polymorphisms, along with 10 additional genetic polymorphisms via gene-gene interactions, significantly influenced lung cancer risk potentially associated with PAH inhalation exposure. Most polymorphisms were associated with PAH metabolism. According to the established genetic susceptibility score (GSS), lung cancer risk increased with a rise in the GSS level, thereby indicating a positive dose-response relationship.

[A study on the differential diagnosis of ciliated epithelial cells from Lophomonas blattarum in bronchoalveolar lavage fluid].

OBJECTIVE: To validate the authenticity of the cases diagnosed as pulmonary Lophomonas blattarum infection in literatures and Lophomonas blattarum as a kind of pathogen resulting in pulmonary infection. METHODS: From June 2012 to May 2013, mobile cells with cilia at the anterior end of the cells were observed in BALF from 6 patients with pulmonary disease in our hospital. Morphological feature and ultrastructure of the cells were further investigated by optical microscope and electron microscope to determine the type of the cells referring to literature-published photos of Lophomonas blattarum. Literatures about Lophomonas blattarum infection were searched with keyword Lophomonas blattarum from Wanfang Data, China National Knowledge Infrastructure (CNKI) and PubMed. Diagnostic methods and figures provided by the literature were carefully reviewed, and the accuracy of diagnosis of pulmonary Lophomonas blattarum was identified. RESULTS: Mobile cells found in BALF from the 6 patients in our hospital had the morphological features of bronchial ciliate epithelial cells. A nucleus far from the cilia was observed in the middle or at the bottom of the cytoplasm, and these cells did not display the characteristic cytological structures of Lophomonas blattarum: calyx, perinuclear tubules and axial filament. Diagnosis of pulmonary Lophomonas blattarum reported in literatures so far were all based on the morphological features of mobile cells with a cluster of flagellate at anterior end of the cell by optical microscopy. None of the authors did further exploration on the ultrastructure of such a kind of cells and compared with features of Lophomonas blattarum described in the literature. All the active cells reported in literatures had the identical morphological features to those found in our investigation. CONCLUSION: In the past 20 years, all the diagnosed cases as pulmonary Lophomonas blattarum infection reported in our country were misdiagnosed. Currently, there is no evidence to show Lophomonas blattarum as a pathogen resulting in pulmonary infection.

Epidermal growth factor receptor mutations and their correlation with gefitinib therapy in patients with non-small cell lung cancer: a meta-analysis based on updated individual patient data from six medical centers in mainland China.

BACKGROUND: Convincing data on epidermal growth factor receptor (EGFR) mutations in Chinese patients with non-small-cell lung cancer (NSCLC) remain limited. We investigated the relevance of demographic characteristics and EGFR mutations, correlations between the efficacy of gefitinib and EGFR mutations in NSCLC, and to identify individuals who would likely benefit from gefitinib. METHODS: We conducted a meta-analysis based on updated individual patient data from six medical centers in mainland China. Outcome measures included the EGFR mutation status, demographic characteristics, response, and survival. RESULTS: Among 506 patients with NSCLC who received EGFR mutation analysis, the EGFR mutation rate was 30.04%. Patients with adenocarcinoma had a higher mutation rate than those with non-adenocarcinoma (44.1% vs 9.2%; p < 0.00001). The EGFR mutation rate for smokers was 15.1%, lower than that for non-smokers (45.5%) (p < 0.00001). Male patients had a lower mutation rate than female patients (23.1% vs 42.9%; p < 0.0001). Multivariate analysis showed that "adenocarcinoma" and "non-smoker" were independent predictors of EGFR mutations. In a subgroup of 57 patients with complete treatment data, the response rate to gefitinib in the EGFR mutant group was 60.7%, significantly higher than that in the wild-type EGFR group (17.2%) (odds ratio, 5.78; 95% CI, 1.95-17.13; p = 0.002). "EGFR mutation", "adenocarcinoma," and "non-smoker" were independent predictors of response. Overall survival in the EGFR mutant group and the wild-type group did not differ significantly (hazard ratio, 0.60; 95% CI, 0.32-1.12; p = 0.110). "Adenocarcinoma status" was an independent prognostic factor for survival. CONCLUSIONS: In mainland China, "adenocarcinoma" and "non-smoker" are independent predictors for EGFR mutations. Response to gefitinib favors patients with EGFR mutations. The clinical selected populations for gefitinib are non-smokers with adenocarcinoma.

Gefitinib-sensitive mutations of the epidermal growth factor receptor tyrosine kinase domain in chinese patients with non-small cell lung cancer.

PURPOSE: Studies have shown that mutations in the epidermal growth factor receptor (EGFR) tyrosine kinase domain are associated with response of lung cancer to gefitinib (Iressa, AstraZeneca Corp., Shanghai, China). A higher incidence of EGFR mutation was observed in non-small cell lung cancer (NSCLC) patients of Japanese origin compared with those of American origin. However, no data about such mutations in Chinese patients with NSCLC could be obtained. METHODS: Primary NSCLC tissues were obtained for analysis of mutations in exons 18 to 21 of EGFR from a total of 76 patients, of whom 54 did not receive gefitinib therapy and 22 did. PCR products were sequenced directly and mutations were confirmed by an independent PCR and sequence analysis. All types of mutation were cloned and sequenced. RESULTS: A total of 10 types of mutation were found in the series of patients, including two different silent mutations in exon 20 from 11 patients. More than half of the silent mutations (6 of 11) in exon 20 coexisted with other mutations. Mutations were more frequent in adenocarcinoma (17 of 35; 48.6%) compared with squamous carcinoma (1 of 19; 5.3%) among untreated patients. Similar mutations were observed in all seven gefitinib-treated patients with partial response, and no mutations were detected in all eight patients with progressive disease (P < 0.001), except two silent mutations. Three mutations were observed in seven patients with stable disease. CONCLUSIONS: Mutations in the epidermal growth factor receptor tyrosine kinase domain in lung adenocarcinomas from Chinese patients were more frequent than reported previously in lung adenocarcinomas from American patients. Such mutations were well correlated with tumor response to gefitinib.

[Treatment of non-small cell lung cancer with gefitinib].

OBJECTIVE: To investigate the antitumor effects and toxicity of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor gefitinib (Iressa) in advanced non-small cell lung cancer (NSCLC). METHODS: The clinical data and quality of life of 66 patients with NSCLC treated with Iressa orally at the dose of 250 mg/d were reviewed, and the data were analyzed by using logistic analysis, chi(2) test and t test. The impact of treatment on disease-related symptoms and quality of life was evaluated with Chinese version of European Organization for Research and Treatment of Cancer-Quality of Life Core Questionnaire-30 (EORTC QLQ-C30) and QLQ-LC13. RESULTS: Tumor response rate was 33%. Disease control rate, which included both tumor responses and stable disease, was 70%. The mean scores of each functioning scales and global quality of life in QLQ-C30 increased significantly. Response rates were 91% - 100%. Mean scores of disease-related symptoms decreased significantly. Response rates were 73% - 100%. Quality of life and symptom response were correlated with objective tumour response. The 250 mg/day dose of Iressa was well tolerated by patients. The majority of adverse events were grade I or grade II skin rash and diarrhea, which were manageable and reversible. CONCLUSION: Iressa offers a new treatment option providing meaningful tumor control and symptom relief for many patients with advanced NSCLC.

Evaluation of safety and efficacy of gefitinib ('iressa', zd1839) as monotherapy in a series of Chinese patients with advanced non-small-cell lung cancer: experience from a compassionate-use programme.

BACKGROUND: The gefitinib compassionate-use programme has enabled >39,000 patients worldwide to receive gefitinib ('Iressa', ZD1839) treatment. This paper reports the outcome of gefitinib treatment in Chinese patients who enrolled into the 'Iressa' Expanded Access Programme (EAP) at the Peking Union Medical College Hospital. METHODS: Thirty-one patients with advanced or metastatic non-small-cell lung cancer (NSCLC) that had progressed after prior systemic chemotherapy were eligible to receive oral gefitinib 250 mg/day as part of the EAP. Treatment was continued until disease progression or unacceptable toxicity occurred. The impact of treatment on disease-related symptoms and quality of life (QoL) was evaluated with the Chinese versions of European Organization for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC QLQ-C30 and QLQ-LC13). RESULTS: Gefitinib was well tolerated. Adverse events (AEs) were generally mild (grade 1 and 2) and reversible. The most frequent AEs were acneform rash and diarrhoea. Only one patient withdrew from the study due to a drug-related AE. The objective tumour response rate was 35.5% (95% confidence interval [CI]: 18.6-52.3); median progression-free survival was 5.5 months (95% CI, 1.6 to 9.4); median overall survival was 11.5 months (95% CI, 5.6 to 17.3). The QoL response rates for five functioning scales and global QoL varied from 56-88%. The main symptom response rates varied from 44-84%. QoL and symptom response were correlated with objective tumour response. CONCLUSION: Gefitinib demonstrated safety and efficacy as monotherapy in this series of Chinese patients with advanced NSCLC and was also associated with remarkable symptom relief and improvement in QoL. Although clinical trials are needed to confirm these positive findings, the data suggest that treatment with gefitinib may be beneficial for some Chinese patients who do not respond to chemotherapy and have poor prognosis.

[Detection and clinic implication of circulating tumor cell in patients with lung cancer].

Micrometastasis may occur in the early stage of lung cancer and dissemination of lung cancer cells into blood circulation is pivotal for metastasis. Many approaches, such as polymerase chain reaction, magnetic activated cell sorting, flow cytometery, and rare event imaging system, have been developed rapidly. The detection of circulating tumor cells may renew the clinical stage and treatment of lung cancer.